Virtual reality and haptics as a training device for movement rehabilitation after stroke: a single-case study

OBJECTIVE: To investigate whether training in a virtual environment with a haptic device will improve motor function in the left hemiparetic arm of a stroke subject. DESIGN: Single case, A-B-A design. SETTING: University hospital research laboratory. PARTICIPANT: A man in his late fifties (right handed), with a right-hemisphere lesion that caused a deficit in the left upper extremity. INTERVENTION: The subject trained with a 3-dimensional computer game during a 4-week period that consisted of twelve 90-minute sessions. MAIN OUTCOME MEASURES: Three tests (Purdue pegboard test, dynamometer hand-grip strength, upper-extremity test) and a subjective interview were used to evaluate motor performance. RESULTS: Improvements were found in fine manual dexterity, grip force, and motor control of the affected upper extremity. The subject reported that there was a change in his day-to-day use of the upper extremity and that he was able to use it in activities that were previously impossible for him. CONCLUSIONS: Training with virtual reality and haptics can promote motor rehabilitation.     

Bimanual coordination involving homologous and heterologous joint combinations: when lower stability is associated with higher flexibility

Variability in behavior is often put in an unfavorable light as a marker of lack of skill. Here, we provide evidence that increased variability during preferred patterns of coordination is associated with higher flexibility in adopting new patterns. Twelve right-handed subjects performed cyclical bimanual flexion and extension patterns with four homologous and six heterologous joint combinations involving shoulder, elbow, wrist, and finger movements. Preferred (isofrequency) as well as less preferred (multifrequency) coordination patterns were studied. The findings revealed less accurate and less stable 1:1 coordination patterns during heterologous as compared to homologous limb segment combinations. Conversely, coordination patterns with a 2:1 frequency ratio were performed more accurately and more consistently during heterologous as compared to homologous conditions. Accordingly, a lower degree of coupling between effectors during performance of preferred coordination patterns was associated with more successful performance of less familiar patterns. This suggests that variability may promote the creative exploration of new performance modes.     

Comparison of procedures for evaluating laboratory performance in external quality assessment schemes for lead in blood and aluminum in serum demonstrates the need for common quality specifications

BACKGROUND: The different scoring methods used by eight European External Quality Assessment Schemes (EQASs) for occupational and environmental laboratory medicine were compared to develop suitable quality specifications as a step toward harmonization. METHODS: Real results for blood lead and serum aluminum assays, reported by participants in Italian and United Kingdom EQASs, were evaluated according to individual scheme scoring criteria. The same results were then used to produce z scores using scheme-based between-laboratory SDs as the estimate of variability to determine whether simple performance-derived quality specifications produced better agreement among schemes. RESULTS: The schemes gave conflicting assessments of participants' performance, and participants judged to be successful by one scheme could be defined as performing inadequately by another. An approach proposed by Kenny et al. (Scand J Clin Lab Invest 1999;59:585), which uses clinical inputs to set targets for analytical imprecision, bias, and total error allowable, was then used to elaborate quality specifications. CONCLUSIONS: We suggest that the CLIA '88 recommendations for blood lead (+/- 40 micro g/L or +/- 10% of the target concentration, whichever is the greater) could be used as a quality specification, although a revision to +/- 30 micro g/L or +/- 10% is recommended. For serum aluminum, a suitable quality specification of +/- 5 micro g/L or +/- 20% of the target concentration, whichever is the greater, is suggested. These specifications may be used to compare laboratory performance across schemes.     

CYP3A induction by N-hydroxyformamide tumor necrosis factor-alpha converting enzyme/matrix metalloproteinase inhibitors use of a pregname X receptor activation assay and primary hepatocyte culture for assessing induction potential in humans.

A series of N-hydroxyformamide tumor necrosis factor-alpha converting enzyme (TACE)/matrix metalloprotease (MMP) inhibitors were evaluated for their potential to induce human cytochrome P450 3A (CYP3A). Two in vitro assays were used: 1) a cell-based reporter gene assay for activation of the pregnane X receptor (PXR), and 2) a primary "sandwich" culture of human hepatocytes. Approximately 50 TACE/MMP inhibitors were evaluated in the human PXR assay. A range of PXR activation was observed, 0 to 150% of the activation of the known human CYP3A inducer rifampicin. Three TACE/MMP inhibitors were evaluated in rat and human hepatocytes. Significantly higher PXR activation/CYP3A induction was observed in PXR/hepatocyte models, respectively, for (2R,3S) 3-(formyl-hydroxyamino)-2-(2-methyl-1-propyl)-4-methylpentanoic acid [(1S,2S)-2-methyl-1-(2-pyridylcarbamoyl)-1-butyl]amide (GW3333) compared with (2R,3S)-6,6,6-trifluoro-3-[formyl(hydroxy)amino]-2-isobutyl-N-[(1S,2R)-2-methoxy-1-[(1,3-thiazol-2-ylamino)carbonyl]propyl]hexanamide (GW6495) and (2R)-N-[(1S)-2,2-dimethyl-1-[(methylamino)carbonyl]-propyl]-2-[(1S)-1-[formyl(hydroxy)amino]ethyl]-5-phenylpentanamide (GI4023). The CYP3A induction level achieved with GW3333 at a concentration of approximately 10 microM in human hepatocytes was comparable to that achieved with rifampicin at a concentration of 10 microM. The extent of rodent CYP3A induction caused by GW3333 was confirmed in vivo after daily oral administration for 14 days to rats. In conclusion, GW3333 is a potential inducer of CYP3A expression in vivo in humans, but other N-hydroxyformamides are less likely to induce CYP3A.     

Excellent results of HA coating on a grit-blasted stem: 245 patients followed for 8-12 years

We report the outcome of a grit-blasted titanium stem designed for press-fit insertion and entirely plasma sprayed with HA. During the years 1988-1993, we performed 323 primary total hip replacements in 276 patients (189 women) with a HA-coated prosthesis. Their mean age was 48 (15-79) years. During the follow-up, 12 patients died. 19 other patients did not attend the follow-up examination, but had no major symptoms according to telephone interviews and written replies. Thus, 245 patients (291 hips) were followed for a mean of 10 (8-12) years with radiographic and clinical examinations. Only 1 stem was revised due to mechanical failure. None were revised because of infection. Osteolysis was significantly associated with wear, and wear was significantly associated with the size of the femoral head. We found a small amount of proximal bone loss (37/291) and a low incidence of distal hypertrophy of the bone (23/291). These observations indicate an essentially physiological weight distribution from the stem to the femoral bone. The changes in the bone confirmed that the femoral component was well fixed in asymptomatic patients. To conclude, we found excellent 8-12-year results with a fully HA-coated femoral prosthesis designed for press-fit insertion.     

Preliminary studies of offspring exposure to phenylbutazone and ivermectin during the perinatal period in a Holstein cow-calf model

The pregnant Holstein cow and her newborn calf were evaluated as an animal model to study in utero and for lactational drug transfer and offspring exposure. A nonsteroidal antiinflammatory drug, phenylbutazone, and an antiparasitic drug, ivermectin, were tested in the model. Prior to parturition, pregnant cows were dosed orally to steady state with phenylbutazone at 4 g/day or given a single subcutaneous injection of 200 microg ivermectin/kg body wt. The level of drug transferred to calves exposed in utero, in utero combined with lactational exposure, and via lactational exposure only, was measured from days 1 through 7 postpartum. At birth the plasma level in phenylbutazone-exposed calves was approximately one-half the dam's steady-state level. For ivermectin-exposed calves, plasma levels were at or below the limit of quantitation (0.5 ng/ml) at birth, suggesting that placental transfer of ivermectin is limited in the cow. For both drugs, rapid accumulation of the drug in calf plasma occurred with lactational exposure to a mean daily dose of 2 microg ivermectin/kg body wt or 0.1 mg phenylbutazone/kg body wt/day for the first 7 days of life. The accumulation observed in the newborn calf is attributed to the lipid solubility and long elimination half-lives of these drugs. These results demonstrate that drug transfer and offspring exposure can be studied using the cow-calf model. The data also highlight the importance of considering not only the dose but also physicochemical characteristics and pharmacokinetics of the drug in the offspring when evaluating the safety of a newborn's exposure to a drug in breast milk.